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In April 1993, the Agency for Toxic Substances and Disease Registry (ATSDR)
wrote a health consultation on mercury contamination in the East Fork Poplar
Creek flood plain. The finding of the consultation was that mercury contamination
in soil did exist at levels that could pose a health risk to residents in the
area (1).

In January 1994, the U. S. Department of Energy (DOE ) released a report that
provided more sampling data and also suggested a clean-up level of 50 mg/kg
mercury in soil (2). This clean-up level was based on the U. S. Environmental
Protection Agency (EPA) reference dose for mercury and conservative assumptions
about the potential exposure pathway and exposure doses that might occur through that pathway (2).

In June 1994, DOE released an addendum to their original report. They presented
additional sampling data which suggested that the predominant forms of mercury
found in the area were mercuric sulfide and metallic mercury and cited new studies
concerning the lower absorption rates of these forms of inorganic mercury. Based
on this new information, DOE now recommends a higher clean-up level of 180 mg/kg
(3).

Some members of the local community have questioned DOE's shift in clean-up
levels, and, in particular, they have questioned DOE's assumptions concerning
mercury speciation and absorption. Because of these concerns, these community
members requested a consultation from ATSDR on whether the modified clean-up
level will be protective of public health.

In order to evaluate whether the new clean-up level will be protective, we
analyzed the proposed level using a worst case scenario that bypasses the areas
of scientific debate about speciation and absorption.

Our finding is that the 180 mg/kg clean-up level will be protective of public
health.

Until the East Fork Poplar Creek flood plain is remediated, we continue to
recommend the following interim actions to reduce exposures: 1) post signs and
restrict public access to areas with elevated mercury concentrations and 2)
continue the East Fork Poplar Creek fish advisory.

BACKGROUND

1993 ATSDR Health Consultation

The 1993 ATSDR health consultation evaluated the existing health threat posed
by chemical releases into the East Fork Poplar Creek flood plain by reviewing
limited soil, sediment, surface water, air, and groundwater summary data from
the East Fork Poplar Creek Remedial Investigation Report Phase IA and summary
fish data from the DOE Biological Monitoring and Abatement Program. ATSDR concluded
that mercury in soil and sediment in some areas along the East Fork Poplar Creek
flood plain posed a threat to public health, especially to children playing
in the flood plain (1). ATSDR recommended either advising the public that soil
and sediment in the East Fork Poplar Creek flood plain was contaminated with
mercury or restricting access to areas with elevated concentrations of mercury
(1).

1994 DOE Remedial Investigations

In January 1994, DOE released the remedial investigation, which evaluated the
extent and level of contamination in the 100-year East Fork Poplar Creek flood
plain and established a preliminary clean-up level of 50 mg/kg (milligrams per
kilogram) or ppm (parts per million) mercury in the flood plain soil (rounded
down from 58 mg/kg) to protect children who might eat the soil or come in contact
with it. The preliminary level was based on the U.S. Environmental Protection
Agency (EPA) guidance, EPA reference dose (RfD) for mercury, and site-specific
exposure assumptions (2).

In June 1994, DOE released an addendum to the remedial investigation, which
presented the results of additional studies of mercury in the East Fork Poplar
Creek flood plain soil. In the addendum DOE stated that several different analytical
methods indicated that mercuric sulfide and metallic mercury are likely to be
the dominant inorganic mercury forms present and that mercuric chloride (the
most easily absorbed and the most toxic inorganic form of mercury) is a minor
component of the total mercury in the East Fork Poplar Creek flood plain soils
(3). DOE also stated the weight of evidence supports their hypothesis that these
predominant forms of mercury in the flood plain soil are less soluble, less
bioavailable (not as easily absorbed into the bloodstream), and less toxic than
the highly soluble mercuric chloride used to develop the preliminary clean-up
level (3). Based on this evidence, DOE recommended a higher clean-up level of
180 mg/kg mercury in soil by reducing the bioavailability factor in their calculations
from 100 to 30 percent (3).

Request for Health Consultation

Some local residents are concerned about the new recommended clean-up level.
In particular, they have questioned DOE's assumptions concerning the speciation
and bioavailability of mercury in the flood plain soil. These citizens have
asked ATSDR to evaluate whether the recommended clean-up value of 180 mg/kg
mercury in the East Fork Poplar Creek flood plain soil will be protective of
public health.

To evaluate whether the recommended mercury clean-up level is protective, we
bypassed the areas of scientific debate about speciation and bioavailability
of mercury in the flood plain soil and analyzed the 180 mg/kg mercury clean-up
level using a worst case scenario.

WORST CASE SCENARIO

This scenario evaluated young children who live close to East Fork Poplar Creek
and play in the East Fork Poplar Creek flood plain soils during the early years
of life. This worst case exposure scenario was selected because it uses the
most sensitive population (young children) exposed to the most highly absorbable
form of inorganic mercury (mercuric chloride and metallic mercury) by the most
probable exposure routes. The most probable route of exposure to inorganic mercury
in soil would be swallowing dust and dirt, and the primary route of exposure
to metallic mercury in soil would be breathing mercury vapors in the air (4).

Mercury in Soil

We estimated a child would receive 0.001 mg/kg/day of mercury during the early
years of life (milligrams of mercury for every kilogram of the child's body
weight everyday) if the child daily swallowed a small amount of dirt (e.g.,
from mouthing toys or fingers with dust on them) containing 180 mg/kg mercuric
chloride(1). We used mercuric chloride in our calculations because studies have
shown it is highly soluble and more of it will be absorbed across the stomach
and walls of the intestine than other forms of inorganic mercury. To determine
if this "worst case" dose poses a health hazard, we then examined
recent U. S. Public Health Service studies of animals fed mercuric chloride.

Animal studies have been used to define a no-observed-adverse-effect level
(NOAEL) of 0.23 mg/kg/day for intermediate exposure (more than fourteen days
but less than one year) to inorganic mercury and a lowest-observed-adverse effect
level (LOAEL) of 1.9 mg/kg/day for chronic exposure (more than one year) to
inorganic mercury (4, 5). The NOAEL is the amount of mercury animals ingested
five days a week for six months without any adverse health effect (4, 5). The
LOAEL is the smallest amount of mercury animals ingested over a lifetime (i.e.,
five days a week for two years) that produced an adverse health effect (4, 5).
For inorganic mercury, the adverse effects first observed in the animals were
minor changes in the kidneys and weight loss. More serious kidney effects were
seen at a higher dose of mercury. Our calculated chronic oral exposure dose
of 0.001 mg/kg/day for children is approximately 1,900 times less than the chronic
LOAEL of 1.9 mg/kg/day and 230 times less than the intermediate NOAEL of 0.23
mg/kg/day. Thus, our estimated chronic oral exposure dose for the worst case
scenario is much lower than the LOAEL and NOAEL.

Mercury in Air

In our evaluation of the danger of inhaling mercury vapor from the flood plain
soil, we considered the air concentrations of mercury vapor that were measured
over flood plain areas with the maximum mercury concentrations in soil. Long-term
air monitoring indicates the concentration of mercury vapor ranged from 0.0000031
to 0.0000124 mg/m3 (milligrams of mercury per cubic meter of air) in air over
soil containing up to 3,000 mg/kg mercury (milligrams of mercury per kilogram
soil) (2). To determine the health hazard of inhaling mercury vapor, we examined
studies of people occupationally exposed to metallic mercury vapor (the most
toxic form for inhalation). A chronic occupational human study was used to define
the lowest-observed-adverse-effect level (LOAEL) of 0.026 mg/m3 for chronic
exposure to mercury vapor in air (4, 6). In that study the adverse effect observed
was an increase in the fine tremors that all people have normally. There is
also some indication from other studies that some memory loss and mild kidney
effects may occur at this LOAEL. The maximum concentration of mercury vapor
measured in air over the flood plain (0.0000124 mg/m3) is 2000 times less than
the LOAEL of 0.026 mg/m3 (2, 4, 6). Thus, air concentrations of mercury vapor
over flood plain soil at its present level of contamination are much lower than
the LOAEL. The air concentrations of mercury vapor over soil with only 180 mg/kg
mercury will be even lower.

DISCUSSION

Exposure Routes

We have considered a worst-case scenario involving children who are exposed
to mercury in East Fork Poplar Creek flood plain soil at a clean up level of
180 mg/kg of mercury. Our assumptions provide a substantial margin of safety
in assessing the health hazard to the community.

The residential land use scenario provides the maximum opportunity for chronic
exposure to the mercury in the East Fork Poplar Creek flood plain soil. Young
children in the residential areas have the greatest risk of exposure to mercury
because they are likely to have the most frequent and longest duration exposure
to East Fork Poplar Creek soils since they play in the dirt and engage in frequent
hand to mouth activity and often mouth objects.

The frequency and duration of exposure to East Fork Poplar Creek flood plain
soil is likely to be much less for older children and adults in general and
particularly for people who do not live on the flood plain. Within the commercial,
DOE, and recreational (e.g., sportsman club and golf course) areas, access to
the flood plain is either difficult or restricted. Within the agricultural areas,
people intermittently enter the flood plain. Consequently, people would more
probably have infrequent and short-duration exposures to mercury via ingestion
of inorganic mercury in soil or inhalation of mercury vapors in the air.

Ingestion of Mercury From Soil

We believe the proposed clean-up level of 180 mg/kg of mercury in East Fork
Poplar Creek flood plain soil will pose no health threat to children or adults.

Swallowing dirt is the most probable route of exposure to inorganic mercury
compounds in the East Fork Poplar Creek flood plain. The hazard from ingesting
inorganic mercury is primarily based on absorption into the bloodstream (internal
dose). Different forms of inorganic mercury compounds (mercuric chloride and
mercuric sulfide are different "forms" of mercury) have different
absorption rates. Most of our information on absorption of inorganic mercury
after ingestion is from animal studies that used mercuric chloride.

We do not have any direct measures of the amount of mercury that children would
absorb (7, 8). No laboratory studies are available on the percent absorption
of inorganic mercury from the gastrointestinal tract in humans (4). However,
we know mercury can be absorbed by this route because mercury has been detected
in humans who have ingested inorganic mercury compounds (mercuric nitrate, mercuric
chloride, mercuric sulfide) (14, 15, 16).

Detailed animal studies indicate absorption of inorganic mercury across the
gut is limited and is influenced by the form of mercury and by an animal's age
and diet, as well as its species. For example, young rats may absorb much more
mercury than old mice. Mercuric chloride, the compound we used for our estimate,
is used in many animal studies because it is very soluble in water and is believed
to have the highest absorption rate of inorganic mercury. The absorption for
mercuric chloride by this route ranges from as little as 1% to as much as 38%
in mice and rats (8, 9, 10). Studies suggest that some forms of mercury, for
example mercuric sulfide, have lower absorption rates or "bioavailability"
through the gut than mercuric chloride (11, 12, 13, 14). However, the relative
bioavailability of mercuric sulfide versus mercuric chloride has not been specifically
studied in animals nor has it been examined in humans (4). On the other hand
we are reasonably certain that absorption is much lower (approximately 0.1%)
for liquid metallic mercury (4). For this reason, ingestion of metallic mercury
is much less hazardous than ingestion of mercuric chloride. In contrast, metallic
mercury is dangerous if its vapor is inhaled, because metallic mercury vapor
is easily absorbed through the lungs (4).

Both animal and human data indicate that, after absorption into the blood,
inorganic mercury compounds go throughout the body but primarily accumulate
in the kidneys (4). In animals, the kidneys had the highest mercury levels following
acute and intermediate oral exposure to mercuric chloride (11). For mercuric
sulfide, higher doses were necessary before accumulation was noted in the kidneys
(11, 13, 14). The accumulation of mercury in the brain and fetuses following
ingestion of inorganic mercury compounds is substantially lower than in the
kidneys because the lipid solubility of inorganic mercury compounds is poor,
which prevents inorganic mercury compounds from crossing the blood-brain and
placental barriers (17). Taken together, these studies have shown that renal
toxicity is the most sensitive end point after ingestion of inorganic mercury.

Basis for Ingestion NOAEL and LOAEL: The no-observed-adverse-effect
level (NOAEL) is a dose of mercury that is based on the highest dose of mercury
for which no adverse health effect has ever been observed in animals. Specifically,
the highest NOAEL of 0.23 mg/kg/day for intermediate oral exposure to inorganic
mercury is based on rats given mercuric chloride in an aqueous solution by gavage
for five days a week for six months (4 ,5). Our calculated worst case oral exposure
dose of 0.001 mg/kg/day for children is approximately 230 times less than
this NOAEL.

The lowest-observed-adverse effect level (LOAEL) is also protective because it's
based on the lowest dose where any adverse effect has been observed in the kidneys
of animals. The intermediate LOAEL of 0.46 mg/kg/day (derived from six-month mercuric
chloride study) is based on a sensitive biomarker for the first appearance of
renal toxicity, increased kidney weight (4, 5). The chronic LOAEL of 1.9 mg/kg/day
for inorganic mercury is based on microscopic changes to certain components of
the kidney as a result of lifetime exposure (thickening of glomerular and tubular
membranes), changes that are likely to indicate more serious effects than kidney
weight change alone (4, 5). This chronic dose is derived from a two-year study
in rats that were exposed a lifetime (i.e., five days a week for two years) to
mercuric chloride in an aqueous solution by gavage (4, 5). Only male rats experienced
an adverse effect in their kidneys at this dose, female rats did not. Furthermore,
although adverse effects were seen in female mice in the same study at a higher
dose (3.7 mg/kg/day), the effects appeared less severe than in males. Taken together,
this and other evidence suggests that male rats may be particularly sensitive
to the effects of mercury exposure. The calculated chronic oral exposure dose
of 0.001 mg/kg/day for children is approximately 460 times less than the
intermediate LOAEL of 0.46 mg/kg/day and 1,900 times less than the chronic
LOAEL of 1.9 mg/kg/day.

It is important to be cautious when generalizing from animal data. NOAELs and
LOAELs based on animal data are not human health guidelines per se. There is
uncertainty in extrapolating from them for the following reasons:

Rat data may not be directly applicable to humans (e.g., humans may be more
sensitive than rats).

Individuals may have different responses (some humans are likely to be
more sensitive than the average).

Using a LOAEL does not give a clear threshold below which adverse effects
do not occur (i.e., we are not sure how much lower than the LOAEL we would
have to go before we would stop seeing the adverse effect entirely).

However, we are confident that the proposed clean-up level of 180 mg/kg of
mercury in the flood plain soil will pose no health threat because the estimated
oral exposure dose is so much lower (2 to 3 orders of magnitude) than the relevant
NOAEL and LOAELs.

We also don't expect adverse effects on other organ systems because the amount
of mercury necessary to cause adverse effects is higher for other organs than
it is for the kidneys. For example, no evidence of neurotoxicity was seen in
mice administrated 0.74 to 2.2 mg/kg/day of mercuric chloride in drinking water
for 110 days and 7.4 to 14.8 mg/kg/day for an additional 400 days (18). Also,
no histopathological evidence of brain lesions was observed in rats receiving
doses of mercuric chloride as high as 3.7 mg/kg/day by gavage, five days a week,
for up to two years, or in mice receiving doses as high as 7.4 mg/kg/day by
gavage, five days a week, for up to two years (4, 5).

Finally our worst case ingestion scenario evaluates all the mercury in the
East Fork Poplar Creek flood plain soil as mercuric chloride, which assumes
that the bioavailability (absorption) of mercury in East Fork Poplar Creek soil
is equivalent to that of mercuric chloride in an aqueous solution. This assumption
is conservative because the majority of mercury forms in the soil are likely
to be less bioavailable than mercuric chloride in aqueous solution. This assumption
provides an additional margin of safety in assuring that exposure to East Fork
Poplar Creek flood plain soil containing 180 mg/kg inorganic mercury will not
result in adverse kidney effects.

Inhalation of Mercury In Air

We believe air concentrations of mercury vapor over the East Fork Poplar Creek
flood plain soil will pose no health threat if soils are remediated to the proposed
clean-up level of 180 mg/kg of mercury.

We predict very little exposure to mercury would take place through inhalation
if soils are cleaned up to 180 mg/kg. However, inhalation is the most toxic
route of exposure to metallic mercury. Therefore, we made conservative assumptions
in the worst case scenario for this exposure route.

The primary route of exposure to metallic mercury in soil is inhalation of
mercury vapors in the air. Once mercury vapors are inhaled, absorption into
the bloodstream is substantial (4). Approximately 74-80% of inhaled elemental
mercury vapor is retained in human tissue (19, 20). Following inhalation, mercury
is distributed throughout the body and accumulates primarily in the kidney,
as it does when ingested. However, the lipophilic nature of metallic mercury
also allows it to readily cross the blood-brain and placental barriers and accumulate
in the brain and fetus (4, 17). Therefore, inhalation is a more toxic route
of exposure.

Basis for Inhalation LOAEL: The central nervous system is the most sensitive
target organ in humans following inhalation of metallic mercury vapor. The lowest-observed-adverse
effect level (LOAEL) of 0.026 mg/m3 for chronic inhalation exposure
to mercury vapors in air is based on a study in which a significant increase
in the average velocity of naturally occurring tremors was observed in workers
exposed to mercury vapors (0.026 mg/m3 average concentration) for
an average of 15.3 years (range 1-41 years) (6). The range of mercury concentration
(0.0000031 to 0.0000124 mg/m3) measured in the air over flood plain
soil containing 3,000 mg/kg mercury is over 2,000 times less than the LOAEL
of 0.026 mg/m3 (2, 4). Since air concentrations of mercury vapor
over soil at 3,000 mg/kg mercury will be much higher than over soil at 180 mg/kg
mercury, we think chronic exposure to mercury vapor from the East Fork Poplar
Creek food plain soil with concentrations of 180 mg/kg mercury will not pose
a health threat.

CONCLUSION

We conclude that the proposed soil clean-up level of 180 mg/kg mercury for
the East Fork Poplar Creek flood plain is safe. Our estimated ingestion dose
is orders of magnitude lower than the LOAEL and NOAEL for ingestion developed
from U. S. Public Health Service studies of animals fed mercuric chloride. Also,
the measured concentration of mercury vapors in the air are much lower than
the LOAEL for chronic inhalation of mercury vapors. Consequently we think the
180 mg/kg clean-up level for the East Fork Poplar Creek flood plain soil will
be protective for exposures through ingestion as well as through inhalation.

RECOMMENDATIONS

The following recommendations from ATSDR's previous health consultation should
be implemented or remain in effect:

Continue the East Fork Poplar Creek fish advisory. Ensure that a sufficient number of signs are posted, especially at the confluence of Poplar Creek, to warn the public of the presence of contaminated fish in the creek (1).

1. The estimated oral exposure dose for the worst case scenario assumes a mercury concentration of 180 mg/kg in soil, a soil ingestion rate of 100 mg soil per day, an exposure factor of 1 for exposure everyday, and a body weight of 16 kg for children 1 through 6 years old.